Mesenchymal Stem Cell Therapy Improves Diabetic Cardiac Autonomic Neuropathy and Decreases the Inducibility of Ventricular Arrhythmias

Background: Diabetic cardiac autonomic neuropathy (DCAN) may cause fatal ventricular arrhythmias and increase mortality in diabetics. Mesenchymal stem cells (MSCs) can secrete various cytokines and growth factors exerting neuro-supportive effects. In this study, we investigated the effect of MSC on DCAN in diabetic rats. Methods: Forty rats were divided into normal control, diabetes mellitus (DM) control, MSC treatment (6 x 10(6) MSCs via direct myocardial injection) and MSC-conditioned medium group (100 mu 1 via direct myocardial injection). Immunohistochemistry was used to measure choline acetyltransferase (ChAT, a marker for parasympathetic nerves) and tyrosine hydroxylase (TH, a marker for sympathetic nerves) positive nerve fibres in the ventricular-myocardium. Heart rate variability and programmed electrical stimulation was used to assess the inducibility of ventricular arrhythmias in the animals. Results: Two weeks after MSC treatment, the density of ChAT- and TH-positive nerve fibres in MSCs and MSC-conditioned medium group was higher than in DM control group (P <0.05 or P <0.01). The ChAT/TH ratio in MSC group was higher than in DM control group (0.37 +/- 0.014 vs. 0.27 +/- 0.020, P <0.01). The standard deviation of normal-to-normal R R intervals in MSCs (5.13 +/- 0.69) and MSC-conditioned medium group (4.30 +/- 0.56) was higher than in DM control group (3.45 +/- 0.60, P < 0.05). The inducibility of VAs in the MSC group was lower than in the DM control group. Conclusions: MSC therapy may promote cardiac nerve sprouting and increase the ratio of parasympathetic to sympathetic nerve fibres. It may also suppress the inducibility of ventricular arrhythmias in the diabetic rats. (C) 2013 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier Inc. All rights reserved.